Tailoring nostoclide structure to target the chloroplastic electron transport chain

Barbosa

et al. 2014

J. Agric. Food Chem.

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In a recent paper, we reported the synthesis and photosynthesis-inhibitory activity of a series of analogues of rubrolides. From quantitative structure-activity relationship (QSAR) studies, we found that the most efficient compounds are those having higher ability to accept electrons. On the basis of those findings, we directed our effort to synthesize new analogues bearing a strong electron-withdrawing group (nitro) in the benzylidene ring and evaluate their effects on photosynthesis. However, the employed synthetic approach led to novel cyclopent-4-ene-1,3-diones as major products. Here, we report the synthesis and mechanism of action of such cyclopent-4-ene-1,3-diones as a new class of photosynthesis inhibitors. These compounds block the electron transport at the QB level by interacting at the D1 protein at the reducing side of Photosystem II and act as Hill reaction inhibitors, with higher activity than the corresponding rubrolides. To the best of our knowledge, this is the first report on the photosynthesis inhibitory activity of cyclopentenediones.

Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cyclopent-4-ene-1,3-diones: A New Class of Herbicides Acting as Potent Photosynthesis Inhibitors

Barbosa

et al. 2014

J. Agric. Food Chem.

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Crystal Growth & Design

“…As part of our ongoing research program focused on the discovery of new bioactive compounds using butenolides as leading building blocks, − similar to the experimental antiepileptic drug losigamone, we further expanded our research on preparing new derivatives of tetronamides aimed at the preparation of a library of compounds for biological investigation . Aiming to better understand the structural features of such compounds to support further structure–biological activity studies, in the present work we describe details of the crystal structures of nine 5-monosubstituted tetronamides ( 1 – 9 ), one 5,5-disubstituted tetronamide ( 10 ), and one parent tetronamide without a substituent at the 5-position ( 11d ) (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Substituent-Modulated Conformation and Supramolecular Assembly of Tetronamides

Karak

Acosta

Barbosa

et al. 2016

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The crystal structures of nine compounds (1−9) bearing the 4-aminofuran-2(5H)-one scaffold (commonly known as tetronamide, C 4 H 5 NO 2) and two decorating aromatic/ heteroaromatic moieties with two stereocenters have been determined. Tetronamides bearing at the 5-position a phenyl moiety (1 and 2, 3-chloro derivatives with either a 4-p-tolylamino or 4-p-bromophenylamino substituent), an o-bromopyridyl moiety (3, a 3-bromo-4-p-tolylamino derivative), or an o-tolyl moiety (4, a 3-bromo-4-p-tolylamino derivative) adopt a U-shaped conformation. This conformation is stabilized by an intramolecular contact involving either the phenyl o-CH moiety (1 and 2) or the substituent at the ortho position (3 and 4) and the π system of the N-phenyl ring. The other five tetronamides (5−9) are not present with such an intramolecular contact. In fact, these last five compounds are not U-shaped and feature the presence at the 5-position of a p-biphenyl moiety (5 and 7, 3-bromo-4-p-tolylamino diastereomers differing as 5R and 5S), a p-methoxyphenyl moiety (6, a 3-chloro-4-pbromophenylamino derivative), or a 5-chlorofuran-2-yl moiety (8 and 9, 3-chloro-4-p-tolylamino diastereomers differing as 5R and 5S). Crystal structures of a 5,5-disubstituted tetronamide bearing m-nitrophenyl moieties (10) and a parent tetronamide without a substituent at the 5-position (11d) reinforce the conformational trend found in 1−9. Furthermore, OH•••O centrosymmetric dimers are formed only in the crystal structures of the U-shaped tetronamides. Chain motifs assembled through OH•••O and NH•••O hydrogen bonds are preferred in the line-shaped tetronamides. Furthermore, the conformer energies were calculated in both the gas and solution phases (B3LYP/6-31G*). The lowest-energy conformations feature an intramolecular N−H•••O hydrogen bond as in the crystal structure of 7. In the U-shaped tetronamides, the crystal structure conformations are similar to the third or fourth energetically ranked stable calculated conformer. Therefore, it is concluded that the substitution pattern in the U-shaped tetronamides allows for accessible secondary minimum-energy conformations that are easily adopted in the crystal structure as a result of their compatibility with the robust centrosymmetric O−H•••O dimer formation.

“…In 2013, König and her group reported the discovery of three new antibiotics from the hitherto unexplored marine myxobacterium Enhygromyxa salina . , The most potent of them, enhygrolide A ( 1 ), exhibited an MIC of 4 μg/mL against Arthrobacter crystallopoietes . Structurally, enhygrolide A features a privileged, densely substituted ( Z )-γ-ylidenebutenolide motif reminiscent of the cyanobacterial metabolites nostoclides I and II ( 2a , b ). − Unlike the nostoclides, enhygrolide A was obtained along with its E -isomer, enhygrolide B ( E- 1 ), although the latter could not be isolated in pure form due to conversion into the more stable Z -isomer 1 . Interestingly, many compounds from this class, natural or otherwise, are endowed with diverse biological properties including antimicrobial, , antitumor, antidiabetic, and herbicidal activities .…”

mentioning

confidence: 99%

Synthesis of the Marine Myxobacterial Antibiotic Enhygrolide A

et al. 2017

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The first synthesis of enhygrolide A, a scarce γ-alkylidenebutenolide antibiotic of the obligate marine myxobacterium Enhygromyxa salina, was achieved in five steps and 54% overall yield from tetronic acid. Key steps include (i) organocatalytic reductive alkylation, (ii) iron-catalyzed sp-sp cross-coupling, and (iii) vinylogous aldol condensation. Aside from its brevity and reliance on environmentally sustainable processes, the synthesis demonstrates the serviceability of butenolide pivalates in cross-coupling reactions.